Probing for affective side effects of drugs used in geriatric practice: use of daily diaries to test for effects of metoclopramide and naproxen.

Author(s): Katz IR, Morales K, Datto C, Streim J, Oslin D, DiFilippo S, Have TT

Affiliation(s): Department of Psychiatry, University of Pennsylvania, Philadelphia, PA 19104, USA. katzi@mail.med.upenn.edu

Publication date & source: 2005-08, Neuropsychopharmacology., 30(8):1568-75.

Publication type: Clinical Trial; Randomized Controlled Trial

The aim of this study was to develop the use of daily diaries of affects and events as measures of pharmacological effects on affective processes and to apply them to evaluate the possible affective toxicity of metoclopramide and naproxen, two medications commonly used in geriatric practice. In all, 105 adults aged 65 years or older were randomized to receive metoclopramide (up to 40 mg/day), naproxen (up to 1000 mg/day), or placebo under double-blind conditions for a period of 5 weeks. Patients were seen weekly for evaluations of affective and cognitive outcomes as well as safety. In addition, patients kept diaries with daily records of positive and negative affect and reports of significant daily events. Findings included mixed model analyses of drug assignment, time, events, and interactions for both positive affect and days with significant negative affect. Subjects exhibited high levels of adherence in completing daily diaries. Neither the pattern of dropouts nor the weekly assessments demonstrated significant drug effects on mood or affect. However, diary data demonstrated that metoclopramide increased the apparent impact of negative events on both positive and negative affect relative to placebo, and that naproxen increased the apparent impact of positive events on positive affect and, possibly, of negative events on negative affect relative to placebo. The findings confirm the utility of diary methods for studying drug effects on affective processes in normal elderly subjects. They suggest that both metoclopramide and naproxen can affect the associations between daily events and affects. If replicated, they would demonstrate that drug effects can extend beyond the intensity of affect and/or the emergence of full-fledged psychiatric disorders to include moderation of the interactions between daily events and affect.